Drugmakers large and small have faced setbacks in advancing potential drugs against non-alcoholic steatohepatitis (NASH). Now that two appear to be nearing the market, the cost watchdogs at the Institute for Clinical and Economic Review (ICER) are weighing in on potential pricing.
Madrigal Pharmaceuticals’ resmetirom fared better than Intercept’s Ocaliva (obeticholic acid) in a draft assessment by ICER looking at potential cost-effectiveness in treating non-alcoholic steatohepatitis.
There are no approved treatments for the disorder which affects between 1.5% and 6.5% of adults in the United States. But several therapies are in development, with FDA decisions possible for resmetirom and obeticholic acid in 2023.
In ICER’s study, an annual placeholder price of $19,000 for resmetirom would provide cost savings over a lifetime of care for NASH patients, ICER said. Meanwhile, Ocaliva’s current list price of $85,000 would need to be reduced dramatically to make it cost-effective.
These findings come in the form of a draft report, which marks the midpoint of an 8-month review process, ICER stressed.
ICER derived its resmetirom pricing placeholder from a 2022 study of potential NASH treatments, the group said. Obeticholic acid's placeholder price is based on its 2022 wholesale acquisition cost in its approved use of primary biliary cholangitis.
In reviewing the findings, Intercept said that it does not believe that ICER's economic model does not "include the full breath of publicly available information" on its drug.
"We believe that the draft Evidence Report fails to fully reflect the potential clinical and economic value of OCA for patients with pre-cirrhotic fibrosis due to NASH, particularly those with advanced fibrosis without cirrhosis," a company spokesperson wrote. "Further, it’s premature for ICER to assign a price to OCA in NASH in this model as a price cannot be determined until after the FDA review process concludes. We continue to work with the FDA as they review our new drug application in consideration of determining the product label."
Both resmetirom and obeticholic acid appear to improve survival and quality of life in NASH, but based on ICER’s analysis of trial data, resmetirom is the more promising treatment.
“Resmetirom appears to reduce progression, promote regression of fibrosis, and lead to resolutions of NASH compared with placebo,” Boston-based ICER wrote.
By contrast, ICER saw a “moderate certainty of small or substantial net benefit” with obeticholic acid and with more potentially negative consequences, citing cardiovascular issues and the incidence of pruritis as a common side effect.
NASH is caused by a buildup of fat in the liver which can lead to inflammation, scarring and cirrhosis. The condition isn’t necessarily progressive. It is similar to the liver disease caused by heavy drinking but NASH occurs in people who don’t abuse alcohol. There is no cure. Diet modification and exercise can slow its progression.
In December, Philadelphia-based Madrigal reported results from a phase 3 study showed that both 80-mg and 100-mg daily doses of resmetirom hit both liver histological improvement endpoints that the FDA had proposed as reasonably likely to predict clinical benefit.
"ICER’s initial draft assessment is aligned with our belief that resmetirom has the potential to be a cost-effective specialty therapy for patients," said Madrigal, which added that it plans to file file a new drug application seeking accelerated approval of resmetirom in the first half of this year.
Obeticholic acid is up for a June decision in NASH, New Jersey-based Intercept said last month, while warning that the date is subject to change.
The drug was rejected by the FDA for use against NASH in 2020 but data from the phase 3 REGENERATE trial showed that obeticholic acid helped patients with advanced but pre-cirrhotic NASH achieve at least one stage of liver scarring improvement with no worsening of NASH after 18 months.
Aside from these potential treatments, multiple other drugs have entered the "NASH graveyard" after failed studies, including Genfit's elafibranor and Gilead’s selonsertib.